The relationship between host defense peptides and adrenal steroids. An account of reciprocal influences.
Díaz. Ariana A; Diab. Magdalena M; Mata-Espinosa. Dulce D; Bini. Estela E; D'Attilio. Luciano L; Bottasso. Oscar O; Hernández-Pando. Rogelio R; Bay. María Luisa ML; Bongiovanni. Bettina B
Key Findings
- Cortisol reduces the production of LL‑37 and other antimicrobial peptides in macrophages exposed to TB bacteria.
- DHEA increases reactive oxygen species and reduces intracellular TB growth, regardless of cortisol presence.
- LL‑37 directly suppresses cortisol and DHEA secretion in adrenal cells and alters steroid‑making enzyme messages.
Practical Outcomes
- High stress (high cortisol) may weaken innate immune defenses, so stress‑reduction strategies could support antimicrobial peptide activity. Supplementing DHEA might enhance ROS‑mediated pathogen killing, but dosing and safety need careful consideration. Using LL‑37 as a supplement could potentially lower cortisol levels, but human data are lacking, so it’s not ready for routine use.
Summary
The study shows that stress hormones like cortisol can lower the body’s natural antimicrobial peptides (LL‑37, HBD‑2, HBD‑3) made by immune cells, while the hormone DHEA can boost reactive oxygen species and help kill TB bacteria. Conversely, adding the peptide LL‑37 to adrenal cells cuts down cortisol and DHEA production. These effects were seen in lab cell cultures, not in people.
Abstract
β-defensins 2 and -3 (HBD-2 and HBD-3) and cathelicidin LL-37 are host defense peptides (HDPs) that play a crucial role in the immune response against mycobacteria. Given our former studies in tuberculosis patients wherein their plasma levels of such peptides correlated with steroid hormone concentrations, we now studied the reciprocal influence of cortisol and/or dehydroepiandrosterone (DHEA) on HDPs biosynthesis and LL-37 on adrenal steroidogenesis. Cultures of macrophages derived from the THP-1 line were treated with cortisol (10<sup>-6</sup>M) and/or DHEA (10<sup>-6</sup>M and 10<sup>-7</sup>M) and stimulated with irradiated M. tuberculosis (Mi) or infected M. tuberculosis strain H37Rv to assess cytokine production, HDPs, reactive oxygen species (ROS) and colony forming units. Cultures of NCI-H295-R adrenal line were treated with LL37 (5, 10, and 15 µg/ml) for 24 h to further measure cortisol and DHEA levels together with steroidogenic enzyme transcripts. In macrophages, M. tuberculosis produced an increase of IL-1β, TNFα, IL-6, IL-10, LL-37, HBD-2, and HBD-3 levels, irrespective of DHEA treatment. Adding cortisol to M. tuberculosis-stimulated cultures (with or without DHEA) decreased the amounts of these mediators, compared to only stimulated cultures. Although M. tuberculosis reduced ROS levels, DHEA increased these values in addition to diminishing intracellular mycobacterial growth (no matter cortisol treatment). In turn, studies on adrenal cells showed that LL-37 reduced the production of cortisol and DHEA besides modifying transcripts for some steroidogenic enzymes. while adrenal steroids seem to influence the production of HDPs, the former compounds are also likely to modulate adrenal biogenesis.
Study Information
pubmed
2023
2023-05-25T00:00:00.000Z
10.1016/j.cyto.2023.156229
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